Abstract
A large measles virus outbreak occurred across Vietnam in 2014. We identified and obtained complete measles virus genomes in stool samples collected from two diarrheal pediatric patients in Dong Thap Province. These are the first complete genome sequences of circulating measles viruses in Vietnam during the 2014 measles outbreak.
GENOME ANNOUNCEMENT
Measles virus is a member of the family Paramyxoviridae and causes measles, a highly contagious infectious disease. Measles mainly affects children age <5 years and was responsible for the deaths of 114,900 individuals in 2014 (1). Although measles vaccination is implemented in the Extended Programme for Immunization in Vietnam, measles virus infection is still prevalent in Vietnam, as demonstrated by a recent outbreak of measles virus in 2014 (2). During this outbreak, measles virus was estimated to have caused 30,000 infections, with 146 deaths (2). Until now, there has been only one report on the genome of a measles virus from Vietnam during this outbreak (3), with 2 short regions of the genome sequenced. No full measles virus genomes are available from Vietnam or Southeast Asia, leaving a large knowledge gap on the genetics of the circulating virus.
As part of a viral surveillance project in the Dong Thap Province (southern Vietnam) (4), a randomly primed deep-sequencing (agnostic sequencing) method (5) was used to document viral infections associated with diarrhea. Briefly, nucleic acid was purified from fecal samples, converted to double-stranded DNA (dsDNA) using random primers (6), and sequenced with Illumina HiSeq to generate 4 million 250-nucleotide (nt) paired-end reads per sample. Reads were trimmed from the 3′ end to a median Phred score of 35, with a minimum length of 175 nt, and de novo assembled using SPAdes version 3.5.0 (7), followed by improve_assembly (8). The work identified two complete wild-type measles virus genomes in stool samples from 2 diarrheal patients enrolled in 2014, during the period when measles was known to be circulating in Vietnam. The complete genomes of the virus isolates are named MVs/DongThap.VNM/06_14 (D8) (accession no. KU728742) and MVs/DongThap.VNM/08_14 (D8) (accession no. KU728743), in agreement with the WHO guidelines for naming measles virus strains (9). The average genome coverage of both viral genomes was 91- and 1,835-fold, respectively, demonstrating sufficient coverage to reliably assemble the complete genomes. Complete genome analysis revealed that the Vietnamese measles viruses share 99% nucleotide identity to the measles strain MVi/Muenchen.DEU/19.13[D8], the closest relative measles virus strain. The genomes have 9- and 19-nucleotide differences, respectively, compared to the measles strain MVi/Muenchen.DEU/19.13 (D8). No nucleotide changes were observed in the 450 nucleotides that encode the carboxy-terminal region of the nucleoprotein, the region used for genotyping.
Both patients were admitted to the Provincial Hospital of Dong Thap due to acute diarrhea, and the generation of whole measles virus genomes from these patients suggests that the episodes of diarrhea reported in these patients may be a consequence of measles virus infection, consistent with previous observations (10). In addition, these patients were 7 and 8 months of age, demonstrating that children can be infected with measles virus before reaching the age of vaccination (9 months). In conclusion, we report the first 2 whole genomes of wild-type measles virus genotype D8 during the 2014 outbreak in Vietnam. The viral genomes belonged to measles virus genogroup D8 and will provide a useful reference for measles surveillance in the region.
Nucleotide sequence accession numbers.
The complete genome sequences of the MVs/DongThap.VNM/06_14 (D8) and the MVs/DongThap.VNM/08_14 (D8) isolates are available at GenBank under the accession numbers KU728742 and KU728743.
ACKNOWLEDGMENTS
The VIZIONS Consortium members (alphabetical order by surname) from the Oxford University Clinical Research Unit are Bach Tuan Kiet, Stephen Baker, Alessandra Berto, Maciej F. Boni, Juliet E. Bryant, Bui Duc Phu, James I. Campbell, Juan Carrique-Mas, Dang Manh Hung, Dang Thao Huong, Dang Tram Oanh, Jeremy N. Day, Dinh Van Tan, H. Rogier van Doorn, Duong An Han, Jeremy J. Farrar, Hau Thi Thu Trang, Ho Dang Trung Nghia, Hoang Bao Long, Hoang Van Duong, Huynh Thi Kim Thu, Lam Chi Cuong, Le Manh Hung, Le Thanh Phuong, Le Thi Phuc, Le Thi Phuong, Le Xuan Luat, Luu Thi Thu Ha, Ly Van Chuong, Mai Thi Phuoc Loan, Behzad Nadjm, Ngo Thanh Bao, Ngo Thi Hoa, Ngo Tri Tue, Nguyen Canh Tu, Nguyen Dac Thuan, Nguyen Dong, Nguyen Khac Chuyen, Nguyen Ngoc An, Nguyen Ngoc Vinh, Nguyen Quoc Hung, Nguyen Thanh Dung, Nguyen Thanh Minh, Nguyen Thi Binh, Nguyen Thi Hong Tham, Nguyen Thi Hong Tien, Nguyen Thi Kim Chuc, Nguyen Thi Le Ngoc, Nguyen Thi Lien Ha, Nguyen Thi Nam Lien, Nguyen Thi Ngoc Diep, Nguyen Thi Nhung, Nguyen Thi Song Chau, Nguyen Thi Yen Chi, Nguyen Thieu Trinh, Nguyen Thu Van, Nguyen Van Cuong, Nguyen Van Hung, Nguyen Van Kinh, Nguyen Van Minh Hoang, Nguyen Van My, Nguyen Van Thang, Nguyen Van Thanh, Nguyen Van Vinh Chau, Nguyen Van Xang, Pham Ha My, Pham Hong Anh, Pham Thi Minh Khoa, Pham Thi Thanh Tam, Pham Van Lao, Pham Van Minh, Phan Van Be Bay, Maia A. Rabaa, Motiur Rahman, Corinne Thompson, Guy Thwaites, Ta Thi Dieu Ngan, Tran Do Hoang Nhu, Tran Hoang Minh Chau, Tran Khanh Toan, Tran My Phuc, Tran Thi Kim Hong, Tran Thi Ngoc Dung, Tran Thi Thanh Thanh, Tran Thi Thuy Minh, Tran Thua Nguyen, Tran Tinh Hien, Trinh Quang Tri, Vo Be Hien, Vo Nhut Tai, Vo Quoc Cuong, Voong Vinh Phat, Vu Thi Lan Huong, Vu Thi Ty Hang, and Heiman Wertheim; from the Centre for Immunity, Infection, and Evolution, University Of Edinburgh: Carlijn Bogaardt, Margo Chase-Topping, Al Ivens, Lu Lu, Dung Nyugen, Andrew Rambaut, Peter Simmonds, and Mark Woolhouse; from The Wellcome Trust Sanger Institute, Hinxton, United Kingdom: Matthew Cotten, Bas B. Oude Munnink, Paul Kellam, and My Vu Tra Phan; from the Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Amsterdam, the Netherlands: Martin Deijs, Lia van der Hoek, Maarten F. Jebbink, and Seyed Mohammad Jazaeri Farsani; and from Metabiota, CA: Karen Saylors and Nathan Wolfe.
This work was supported by the Wellcome Trust of the United Kingdom through the VIZIONS strategic award WT/093724.
Funding Statement
This work was supported by the Wellcome Trust of the United Kingdom through the VIZIONS strategic award (WT/093724).
Footnotes
Citation Oude Munnink BB, Phan MVT, Kellam P, Cotten M, the VIZIONS Consortium. 2016. Complete genome characterization of two wild-type measles viruses from Vietnamese infants during the 2014 outbreak. Genome Announc 4(2):e00250-16. doi:10.1128/genomeA.00250-16.
REFERENCES
- 1.WHO 2015. Measles. Fact sheet no. 286. World Health Organization, Geneva, Switzerland: http://www.who.int/mediacentre/factsheets/fs286/en/. [Google Scholar]
- 2.Roberts L. 2015. In Vietnam, an anatomy of a measles outbreak. Science 348:962. doi: 10.1126/science.348.6238.962. [DOI] [PubMed] [Google Scholar]
- 3.Pham VH, Nguyet DP, Mai KN, Truong KH, Huynh LV, Pham TH, Abe K. 2014. Measles epidemics among children in Vietnam: genomic characterization of virus responsible for measles outbreak in Ho Chi Minh City, 2014. EBioMedicine 1:133–140. doi: 10.1016/j.ebiom.2014.10.015. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Rabaa MA, Tue NT, Phuc TM, Carrique-Mas J, Saylors K, Cotten M, Bryant JE, Nghia HD, Cuong NV, Pham HA, Berto A, Phat VV, Dung TT, Bao LH, Hoa NT, Wertheim H, Nadjm B, Monagin C, van Doorn HR, Rahman M, Tra MP, Campbell JI, Boni MF, Tam PT, van der Hoek L, Simmonds P, Rambaut A, Toan TK, Van Vinh CN, Hien TT, Wolfe N, Farrar JJ, Thwaites G, Kellam P, Woolhouse ME, Baker S. 2015. The Vietnam initiative on zoonotic infections (VIZIONS): a strategic approach to studying emerging zoonotic infectious diseases. Ecohealth 12:726–735 doi: 10.1007/s10393-015-1061-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Cotten M, Oude Munnink B, Canuti M, Deijs M, Watson SJ, Kellam P, van der Hoek L. 2014. Full genome virus detection in fecal samples using sensitive nucleic acid preparation, deep sequencing, and a novel iterative sequence classification algorithm. PLoS One 9:e93269. doi: 10.1371/journal.pone.0093269. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Endoh D, Mizutani T, Kirisawa R, Maki Y, Saito H, Kon Y, Morikawa S, Hayashi M. 2005. Species-independent detection of RNA virus by representational difference analysis using non-ribosomal hexanucleotides for reverse transcription. Nucleic Acids Res 33:e65. doi: 10.1093/nar/gni064. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Bankevich A, Nurk S, Antipov D, Gurevich AA, Dvorkin M, Kulikov AS, Lesin VM, Nikolenko SI, Pham S, Prjibelski AD, Pyshkin AV, Sirotkin AV, Vyahhi N, Tesler G, Alekseyev MA, Pevzner PA. 2012. SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing. J Comput Biol 19:455–477. doi: 10.1089/cmb.2012.0021. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Page AJ. 2012. Improve_assembly. Wellcome Trust Sanger; Institute, Hinxton, United Kingdom. [Google Scholar]
- 9.WHO. 2/3/2012 Measles virus nomenclature Update: 2012. Wkly Epidemiol Rec 87:73–80. [PubMed] [Google Scholar]
- 10.Varavithya W, Aswasuwana S, Phuapradit P, Louisirirotchanakul S, Supavej S, Nopchinda S. 1989. Etiology of diarrhea in measles. J Med Assoc Thai 72(Suppl 1):151–154. [PubMed] [Google Scholar]